Multi-parameter sensor apparatus

ABSTRACT

A multi-parameter catheter comprising sensors enveloped in a sheath made from a biphasic material comprising a layer of microporous hydrophobic substance having micropores which are filled with a hydrophilic substance which when hydrated forms a gel and allows the passage of water-bound ions, and an apparatus for introducing the catheter into a patient&#39;s blood vessel.

This is a division of application Ser. No. 08/085,844, filed on Jun. 30,1993, now abandoned.

FIELD OF INVENTION

This invention relates to a material which exhibits both hydrophobic andhydrophilic characteristics, defined herein as a "bipbasic" material.More particularly, the invention relates to a biphasic material in theform of a flat or tubular membrane, hereinafter referred to as abiphasic membrane. The invention is also concerned with a cathetercontaining multi-parameter sensors, herein designated a multi-parametercatheter, having an outer wall at least part of which is made from abiphasic membrane; an apparatus comprising such a catheter incombination with a device for introducing the catheter into a patient'sblood vessel and a vacuum rig apparatus for introducing a liquid into adesired space.

BACKGROUND OF THE INVENTION

Invasive sensors for determining the concentration of various analytesin body fluids, particularly the concentration of gasses such as oxygenand carbon dioxide in blood, have been proposed in the art.

U.S. Pat. No. 3,905,888 discloses an electrochemical sensor fordetermining the oxygen partial pressure in a biological mediumcomprising a flexible plastic tube which is permeable to oxygen andhouses a pair of electrodes surrounded by an electrolyte.

Sensors for the determination of pH and pCO₂ normally comprise one ormore optical fibers in association with a suitable indicator for theparameter under investigation.

U.S. Pat. No. 4,200,110 discloses a fiber optic probe which includes anion permeable membrane envelope which encloses the end of a pair ofoptical fibers. The operation of the probe depends upon the opticaldetection of a change in color of a pH sensitive dye. U.S. Pat. No.4,943,364 discloses a fiber-optic probe for measuring the partialpressure of carbon dioxide in a medium comprising a hydrolyzed dye/gelpolymer in contact with a bicarbonate solution enveloped in a membranecovering the distal end of the fiber.

U.S. Reissue Pat. No. Re 31,879 discloses a method for measuring theconcentration of an analyte in a sample which involves measuring achange in the color characterization of a fluorescent indicator attachedto an optical fiber, without or with a gas-permeable membrane.

Commonly assigned U.S. Pat. No. 4,889,407 discloses an optical waveguidesensor for determining an analyte in a medium, which sensor comprises anoptical waveguide having a plurality of cells arranged in an array whichsubstantially covers the cross-sectional area of the waveguide, each ofsaid cells containing an indicator sensitive to said analyte.

When a probe, such as one of those disclosed in the above prior art, isused invasively, it is usually introduced into a body lumen, for examplea blood vessel, with the aid of an introducer and, to protect the probeitself, avoid contamination, maintain sterility and also facilitateintroduction, the probe is usually accommodated within an elongatedtubular catheter.

The prior art patents mentioned above disclose sensors adapted todetermine a single analyte. However, there is a need in the art for asingle device which is capable of determining and monitoring a number ofblood parameters, for example, pH, pO₂, pCO₂ and temperature, and whichhas a small enough diameter to be inserted into a blood vessel.

U.S. Pat. No. 4,727,730 discloses a blood pressure monitoring apparatuscomprising a single fiber probe that interrogates three dye wells eachusing a fluorescent dye. Blood pressure is monitored with the aid of adiffraction grating.

U.S. Pat. No. 4,854,321 discloses a single probe having multiple dyewells for monitoring blood gases.

U.S. Pat. No. 4,279,795 discloses a hydrophilic-hydrophobic graftcopolymer formed by the copolymerization of a free radical polymerizablevinyl monomer capable of forming a hydrophilic polymer and a hydrophobicmacromolecular compound.

By using a biphasic membrane as described and claimed herein, it ispossible to incorporate sensors for the determination and monitoring ofpH, pO₂, pCO₂ and temperature in a single multi parameter catheter whichis narrow enough to be inserted safely into a patient's blood vessel.

Since it is important to avoid contamination and direct operator contactwhen introducing the catheter into a patient's blood vessel, theinvention also provides a device, or introducer, for said introduction.

U.S. Pat. No. 4,906,232 discloses an intravascular delivery devicecomprising seal means, a delivery assembly having an inner sleeve andstop means.

U.S. Pat. No. 4,960,412 discloses a valve assembly for a catheterintroducer.

It has now been found that optimum results are obtained from amulti-parameter catheter if at least part of the tubular wall or outersheath of the catheter is made from a biphasic membrane as disclosedherein.

SUMMARY OF THE INVENTION

In accordance with the present invention there is provided a biphasicmaterial comprising a layer of microporous hydrophobic substance havingmicropores which are filled with a hydrophilic substance which whenhydrated forms a gel and allows the passage of water-bound ions.

In a preferred embodiment, the layer of microporous hydrophobicsubstance is a membrane made from a hydrophobic polymer, for examplepolyethylene, which may be flat or tubular. The substance allows thepassage of gasses but, because of its hydrophobicity, the passage ofliquid water bound molecules or ions is not possible. Since hydrogenions require liquid water molecules for transport, the membrane is alsoimpermeable to hydrogen ions. To make the microporous membrane permeableto hydrogen ions, the micropores, a typical size for which is 0.1micron, are filled with a hydrophilic substance, for example apolyacrylamide, which when hydrated forms a gel and allows the passageof water-bound ions. Thus the membrane is biphasic, i.e. bothhydrophobic and hydrophilic.

Due to their high water content, many hydrogels are inherentlybiocompatable. Also, a hydrogel provides a medium which is permeable tolow molecular weight molecules, ions, and gases; although it inhibitsthe transfer of high molecular weight blood components, which wouldinterfere with the performance of sensors. This combination ofproperties make a hydrogel satisfactory for use in invasive sensors,particularly pH sensors. However, in general, hydrogels are mechanicallyweak. This latter disadvantage is overcome by the present inventionwherein a preferred hydrogel is incorporated into a microporous layer ofsubstance having the desired mechanical strength to be used as the outersheath or wall of an invasive catheter. The hydrogel fills themicropores of the microporous layer.

The preferred substance for the microporous layer is high densitypolyethylene, which is a hydrophobic substance. Another substance whichmay be used for the microporous layer is polypropylene.

A preferred use for the biphasic membrane of the present invention is asthe outer wall of a catheter containing multi-parameter sensors asdescribed hereinafter.

Accordingly, the invention also provides a multi-parameter catheter forthe in vivo determination of multiple parameters in a patient's bloodcomprising an elongated tube with a distal hollow chamber terminating ina distal end, the wall of said chamber being defined at least in part bya biphasic membrane made from a layer of microporous hydrophobicsubstance having micropores which are filled with a hydrophilicsubstance which when hydrated forms a gel which allows the passage ofwater-bound ions and said chamber containing a plurality of sensorsmounted sequentially from said distal end within a hydrophilic medium.

In a preferred embodiment of the catheter the sequentially mountedsensors comprise, in sequence from the distal end of the chamber, anoptical fiber Ph sensor, an optical fiber pCO₂ sensor, a thermocoupletemperature sensor and a pO₂ sensor. The pO₂ sensor may be anelectrochemical pO₂ sensor as described herein or a fluorescent pO₂sensor.

Preferably the biphasic membrane is a microporous polyethylene tubehaving micropores which are filled with a polyacrylamide hydrogel, thehydrophilic medium within which the sensors are mounted is apolyacrylamide hydrogel and the distal end of the chamber is sealed by asolid plug made from a thermoplastic polymer.

The invention also provides an apparatus for the in vivo determinationof multiple parameters in a patient's blood comprising, in combination,a catheter as described above and a device for introducing the catheterinto a patient's blood vessel, which device comprises a first elongatedflexible hollow tube having a distal end, a proximal end and a distalportion terminating in said distal end, a second elongated extensiontube concentrically mounted within the distal portion of the first tubefor telescopic extension beyond the distal end of the first tube andretraction within the first tube, so that when the second tube is fullyextended it completely envelopes the catheter and when it is retractedthe catheter is exposed, the device also including locking means forlocking the second tube in the extended or retracted position asdesired, and means for introducing a sterile liquid within said secondtube to surround the catheter when it is within the tube.

In the above apparatus the introducer device preferably has a connectorat the proximal end thereof, which connector is attached to leads fromeach sensor of the catheter. The connector is adapted to form a junctionwith another connector attached to a suitable monitor for monitoring theparameters under investigation by the sensors. Preferably the junctionformed by the connectors is protected by a barrier as described andclaimed in commonly assigned U.S. Pat. No. 5,230,031.

The invention further provides a vacuum rig apparatus for introducing aliquid into a space defined by a shaped article, which apparatuscomprises a series of interconnected vessels attached through a port toa vacuum line, the vessels comprising a first vessel connected to asecond vessel, which second vessel is adapted to hold said shapedarticle and is a hollow tube with a proximal end and a distal end, saiddistal end being integral with a "U" shaped tube having an open distalend which projects into a space defined by a third vessel which is areservoir for liquid and has a distal end with a first port and a secondport, said first port providing a drain adapted to be plugged or openedas desired and said second port connected to a fourth vessel havingfirst and second sealable ports and a third port for connecting theapparatus to a vacuum line and a tubular conduit connecting the secondvessel, from a port adjacent the proximal end thereof, to the fourthvessel, so that said conduit, second vessel, "U" shaped tube, thirdvessel and fourth vessel form a closed circuit, the apparatus beingtiltable about a point midway along the second vessel so that liquid inthe reservoir initially at a level below the end of the "U" shaped tubeflows into and along the "U" shaped tube into the second vessel tosurround the shaped article and fill the space therein when a vacuum isapplied to the apparatus.

Preferably, the connection between the first vessel and the secondvessel is a tubular conduit which provides a releasable fluid-tightconnection from a port in the first vessel to a port at the proximal endof the second vessel.

The vessels of the vacuum rig apparatus have transparent walls which maybe made of glass or a transparent plastic.

In a preferred embodiment of the apparatus the tubular second vessel isperpendicular to the third vessel which also is preferably tubular inshape; and the tubular conduit connecting the second vessel to thefourth vessel is preferably diagonal with respect to the third vessel.

The vacuum rig apparatus may be used for filling a chamber of amulti-parameter catheter with a hydrophilic medium in which case the"shaped article" is the tubular chamber which houses the sensors of thecatheter and the space defined thereby is the space surrounding thesensors, and the liquid in the reservoir is a hydrogel-forming liquid.The apparatus also may be used for filling the cells in an optical fiberpH sensor or pCO₂ sensor; and for introducing the electrolyte into anelectrochemical pO₂ sensor.

The vacuum rig apparatus additionally may be used to introduce ahydrophilic substance into the micropores of a microporous substrate toform a biphasic membrane according to the invention.

Accordingly the invention still further provides a method forintroducing a liquid into a space defined by a shaped article whichcomprises placing the shaped article in a vessel which is part of avacuum rig apparatus comprising a liquid reservoir perpendicular to thevessel, introducing liquid into the reservoir, applying a vacuum to thevessel to evacuate gas from the space, tilting the apparatus so thatliquid from the reservoir enters the vessel and fills the space.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be more particularly described with reference topreferred embodiments illustrated in the accompanying drawings, inwhich:

FIG. 1 is a schematic side view, partly in cross-section, of amulti-parameter catheter having an outer sheath embodying a biphasicmembrane made from the biphasic material according to the invention;

FIG. 2 is an enlarged side view of a pH sensor included in the catheterof FIG. 1;

FIG. 3 is an enlarged side view of a pCO₂ sensor included in thecatheter of FIG. 1;

FIG. 4 is an enlarged side view of an electrochemical pO₂ sensorincluded in the catheter of FIG. 1;

FIG. 5 is an enlarged side view of a thermocouple included in thecatheter of FIG. 1;

FIG. 6 is a schematic side view of a preferred device for introducing acatheter of FIG. 1 into a patient's blood vessel.

FIGS. 6A-6D are enlarged views of the device of FIG. 6 showing thefeatures thereof in more detail;

FIG. 7 is a schematic panoramic view of a vacuum rig apparatus; and

FIG. 8 is a view of part of the vacuum rig apparatus in the tiltedposition.

DETAILED DESCRIPTION OF THE INVENTION

A particularly preferred embodiment which utilizes a biphasic membraneaccording to the present invention is a system for determining certainparameters in the blood of a patient. The parameters are determined byvarious sensor devices incorporated in a single catheter which isadapted to be inserted into the bloodstream of the patient and, forconvenience, the system is designated herein as a multi-parametercatheter system. The biphasic membrane of the invention is used to format least a part of the tubular wall or outer sheath which envelopes thesensors in the catheter. A device for introducing the catheter into apatient's blood vessel is also described.

Commonly assigned U.S. Pat. No. 4,889,4907, acknowledged above,describes and claims an optical waveguide sensor for determining ananalyte in a medium, for example, blood, which sensor comprises anoptical waveguide, preferably an optical fiber, having a portion to bebrought into contact with said medium, said portion having a pluralityof cells arranged in an array which substantially covers thecross-sectional area of the fiber, each of the cells containing anindicator sensitive to the analyte. This sensor is particularly suitablefor the determination of pH and pCO₂ in blood, and, preferably, a sensoras described and claimed in U.S. Pat. No. 4,889,407 is incorporated inthe multi parameter catheter system utilizing the biphasic membrane ofthe present invention.

FIG. 1 of the accompanying drawings illustrates a multi-parametercatheter 1 comprising a hollow tube defined by a distal portion sheath 2terminating in a distal end 3 which is sealed by a thermoplastic polymerplug 4 to form a closed chamber 5. The preferred method for sealing thetube with a thermoplastic polymer plug and the resulting tubularassembly is described and claimed in commonly assigned U.S. patentapplication Ser. No. 887,993 (U.S. Pat. No. 5,280,130). The proximalportion wall 6 of the tube is made from solid non-porous polymerictubing, for example, polyethylene tubing, and the distal end thereofforms a butt-joint with the sheath 2.

The sheath 2 is a biphasic membrane comprising a layer of a microporoushydrophobic substance the micropores of which are filled with ahydrophilic hydrogel. Also, since the sheath portion of the catheterwill be in contact with body fluids, particularly blood, when thecatheter is in use, preferably heparin is covalently bound to the outersurface thereof to prevent blood clots.

Preferably the microporous substance is a high density polyethylene andthe sheath is a microporous polyethylene hollow fiber (MPHF) with aninternal diameter of from about 425 to 475 microns, a maximum externaldiameter of about 500 microns, and a porosity of about 40%. Thepreferred hydrophilic substance which fills the micropores of the MPHFis a polyacrylamide hydrogel. The method of filling the micropores withthe hydrogel is described hereinafter.

Mounted within the tube, in sequence from the distal end are foursensors, a pH sensor 7, a pCO₂ sensor 8, a temperature sensor 9, and apO₂ sensor 10. The sensors are mounted in the desired staggeredrelationship primarily to reduce the diameter of the catheter. This isbecause the distal end or tip of each sensor is flared, even though theflare is not immediately apparent at the scale shown in the drawings,and adjacent side-by-side alignment would result in an unacceptableincrease in diameter at the tips of the sensors. Also, in the case ofthe pH and pCO₂ sensors, it is desirable to stagger the positioning ofthe cells in the optical fibers to avoid possible interference ofsignals.

The preferred staggered sequence of sensors is illustrated in FIG. 1;but other sequences are also possible for operable sensors.

Within the chamber 5 the sensors are surrounded by a hydrophilic medium,preferably a polyacrylate hydrogel containing phenol red indicator. Asimilar polyacrylate/phenol red hydrogel is impregnated into the cellsof the pH sensor.

If desired the sensors may be secured within the catheter by an adhesiveplug (not shown).

To reduce interference or noise from extraneous radiation the proximalportion of the catheter is back-filled with a radiation-opaque coating12, for example of carbon black, the distal end of the opaque coatingbeing adjacent to the distal end of the solid polyethylene tubing 6.Preferably, the catheter is coated by applying a suspension of carbonblack in silicone, previously de-gassed, through a syringe in a mannerknown in the art. The coating is cured by heating in an oven at 40° C.for about 2 hours. Curing is conducted at the sensor end first toprevent tracking of carbon black into the sensors. Alternatively, thecoating may be an UV-curing silicone rubber containing carbon black andthe curing is conducted at a suitable UV intensity.

The portion of the catheter proximal to the portion containing thesensors has an outer sheath of polyethylene tubing 13.

The individual sensors are illustrated in more detail in the enlargedviews of FIGS. 2-5.

FIG. 2 illustrates a preferred pH sensor 7 which comprises an opticalfiber 14 having a helical array of cells 15 which substantially coversthe cross-sectional area of the fiber. The number of cells in the arraymay vary up to any desired maximum. Preferably the pH sensor of theinvention contains five cells. Each of the cells contains a pH sensitiveindicator, preferably phenol red in a gel. The filling of the cells isaccomplished by use of a vacuum rig apparatus as described herein. Thistype of sensor is described and claimed in U.S. Pat. No. 4,899,407.Optical radiation transmitted along the fiber is reflected by a mirror16 embedded close to the distal end 17 of the fiber and the emittedsignal is returned along the fiber and through the indicator-containingcells to an appropriate monitor which interprets the signal to give anindication of the pH of the medium around the distal portion of thecatheter. An optical fiber sensor having an embedded mirror is describedand claimed in commonly assigned U.S. patent application Ser. No.887,457 (U.S. Pat. No. 5,257,338)

FIG. 3 illustrates a preferred pCO₂ sensor 8 which comprises an opticalfiber 18 having an array of cells 19 which substantially covers thecross-sectional area of the fiber and a mirror 20 embedded close to thedistal end 21. These features are similar to those in the pH sensordescribed above. However, the preferred number of cells in the pCO₂sensor is three and each of these cells is filled with an appropriateindicator, preferably phenol red, in a solution which is a source ofbicarbonate ions. Preferably the solution is sodium carbonate which isconverted to the bicarbonate after incubation. The sensor is envelopedby a tubular membrane 22 of carbon dioxide-permeable polymer, preferablypolyethylene.

FIG. 4 illustrates an electrochemical pO₂ sensor 10 comprising twoelongate insulated conductors 23,24, each having a stripped distalportion, the exposed metal of which provides an active surface formingan anode 25 and cathode 26, respectively. Preferably the anode has alonger active surface than the cathode. In the embodiment illustrated inFIG. 4 the insulated conductor forming the anode is folded into a "U"shape 27 such that the distal end surface of the anode faces the distalend surface of the cathode. The advantage of this configuration is thatit reduces or eliminates the consumption of uninsulated metal from theactive surface of the electrodes other than the distal end thereof,which was a problem frequently encountered in prior art electrochemicalcells. An electrochemical pO₂ sensor such as that illustrated in FIG. 4is described and claimed in commonly assigned U.S. patent applicationSer. No. 07/887,615 (U.S. Pat. No. 5,262,037). An alternative embodiment(not illustrated) which overcomes the above described problem is anelectrochemical cell in which the electrodes are aligned insubstantially parallel relationship alongside each other, again with theactive surface of the anode being longer than the active surface of thecathode, and wherein the insulated portion of the conductor is coveredor coated with an additional layer of insulation. This double insulationprevents short-circuiting caused by pinholes or other defects in theoriginal (single layer) insulation.

In the preferred embodiment the anode and cathode are made of silverwire. Other conductors, such as platinum may be used.

The anode and cathode are contained within a compartment 28 defined byan oxygen gas permeable membrane 29 that permits oxygen to diffusetherethrough. The distal end of the compartment is sealed with a plug 30made from a thermoplastic polymer. The gap 31 between the anode and thecathode, as well as the rest of the compartment surrounding theelectrodes, is filled with an electrolyte, for example a bufferedpotassium chloride aqueous solution. The electrochemical cell formed bythe anode, cathode and electrolyte is an oxygen sensor wherebyconcentration of oxygen in the surrounding medium, for example, blood,is measured by changes in electric current flow across the gap 31. Thecurrent is generated from a source (not shown) connected across theproximal ends of the conductors and changes are measured by a currentmeasuring device in circuit with the source.

FIG. 5 illustrates a temperature sensor 9 which comprises a thermocoupleformed from the stripped distal portion 32 of two insulated metal wires33, 34. The distal ends of the wires are welded together to form awelded tip. Preferably the wires are 0.05 mm. copper wire and 0.05 mm.copper/nickel alloy wire and both wires are insulated with apolyurethane coating 36. The stripped portion of the wires is envelopedby a plastic sleeve 37. The thermocouple temperature sensor is aconventional device in the art.

The multi-parameter catheter described above and illustrated in FIG. 1of the drawings is adapted to be introduced into a blood vessel of apatient, through a cannula previously inserted in the vessel, with theaid of an introducer device such as that illustrated in FIG. 6 of thedrawings.

FIG. 6 schematically illustrates an apparatus comprising the combinationof a catheter 1 and an introducer device 60. The introducer comprises afirst elongated flexible hollow tube 61 having a distal end 62 and aproximal end 63, and a second elongated extension tube 64. The secondtube has an outer diameter the same as or slightly less than the innerdiameter of the first tube, and the second tube is concentricallymounted within a distal portion of the first tube so that it may betelescopically extended beyond the distal end of the first tube orretracted within the distal portion of the first tube. The variouspositions of the extension tube relative to the catheter are illustratedin FIGS. 6A-6D.

The introducer also comprises, at its distal end, a male luer nozzle 65associated with a rotatable locking collar 66. The luer is adapted toconnect the distal end of the introducer to a tonometer (not shown) inwhich the sensor-containing distal portion of the catheter is stored andcalibrated prior to use. The introducer is locked to the tonometer bytightening the collar 66 and released from the tonometer by looseningthe collar.

The introducer further comprises a slidable wing 67 mounted on theextension tube. The slidable wing enables the device to be securelyattached to the body of the patient, preferably by taping, after thecatheter is properly introduced into a blood vessel. A similar wing 68,which may be fixed or slidable, is mounted on the first tube for asimilar purpose.

Located along the second tube and concentrically fixed thereto is a Yjunction 69 having an angled port or outwardly extending arm 70 whichterminates in an obturator 71. The obturator is adapted to be connectedto a source from which sterile liquid may be introduced into the secondtube to surround the catheter when it is within the tube. Sterile liquidis introduced to flush the system and remove air bubbles. Also, theangled port may be used for taking blood samples or monitoring bloodpressure. Thus the extension tube and the associated Y junction make iteasier to access the proximal portion of the catheter away from the siteof insertion. A cannula protects the site of entry of the catheter intoa blood vessel, usually the radial or femoral artery. A clamp nut 72which threadably tightens the Y junction about the second tube throughan O-ring 73 (see FIG. 6D) also acts as a locking means for locking thesecond tube relative to the first tube. The clamp nut has to be loosenedto enable the second tube to be moved telescopically with respect to thefirst tube.

When the second tube is in a fully extended or partially extendedposition relative to the first tube, as indicated, for example, in FIG.6, and FIGS. 6A, 6B and 6D, a portion 74 of the second tube between theclamp nut end the distal end 62 of the first tube is exposed and thisexposed portion preferably has gradations, preferably in cm., to enablethe operator to determine the depth of penetration when the catheter isinserted in a patient's blood vessel. Also located on the exposedportion of the second tube is a removable stop 75 which facilitatespositioning of the catheter when it is inserted in a patient's radialartery. As shown in the cross-sectional view of FIG. 6D, leads 76 fromthe sensors in the catheter, both optical fibers and metal conductors,are connected to terminals 77, i.e. sockets and ferrules, in a connector78. The junction formed by the connector 78 and a cooperating connector(not shown) leading to a monitor for determining the parameters underinvestigation by the sensors is described in U.S. Pat. No. 5,230,031.

FIG. 6 and FIG. 6D show the relative positions of the introducer 64 andthe catheter 1 when the catheter is still in the tonometer (not shown).The catheter is maintained in a sterile environment in the tonometer,which is packaged in a sterile package, such as that described in U.S.patent application Ser. No. 07/888,569 (U.S. Pat. No. 5,246,109), priorto use. When the catheter is to be used it is first calibrated whilebeing retained in the tonometer. After calibration the collar 66 and theclamp nut are loosened so that the tonometer may be removed and thesecond tube be extended forward to envelop the distal portion of thecatheter at the position illustrated in FIG. 6A. Sterile liquidintroduced through obturator 71 and line 70 flushes out tonometersolution, removes air bubbles, maintains a sterile environment aroundthe catheter and prevents contamination from atmospheric contaminants.Also, immediately prior to use heparinized saline solution is introducedto prevent clot formation. The apparatus may be locked in this positionwith the catheter retracted inside the introducer by tightening theclamp nut 72. When the catheter is to be introduced into a patient'sblood vessel, the nozzle is placed within a cannula, previously insertedinto the blood vessel, the clamp nut is loosened and the second tube isretracted back into the first tube thereby allowing the catheter to bethreaded into the cannula. When the removable stop 75 is placed at apredetermined distance along the second tube and the catheter isinserted to a depth so that the stop rests against the distal end of thefirst tube as shown in FIG. 6B this is typically the proper depth forthe radial artery position. When the stop is removed and the second tubeis retracted so that the end of the clamp nut comes to rest against thedistal end of the first tube, as shown in FIG. 6C, this is typically thefemoral artery position. Alternatively, since patients are of differentsizes the operator may determine the proper depth of insertion by usingthe gradations 74 on the second tube. When the catheter is inserted tothe proper position, the clamp nut is tightened, thus locking thecatheter, second tube and first tube and the apparatus is strapped tothe arm or leg of the patient with the aid of the wings 67, 68.

In summary, the apparatus comprising the combination of catheter andintroducer facilitates the introduction of the catheter into a bloodvessel through a cannula whilst minimizing contamination by physicalcontact. The main parts of the introducer are:

(i) The extension tube (second tube) which allows the fixing of variousclinical tubing fittings to be distal from the site of cannulation.

(ii) The Y junction compression fitting which allows reversible hermeticsealing around the catheter. The Y junction also allows the attachmentof pressure lines, blood sampling lines and other accessories.

(iii) The concentric first and second tubes allow the advancement of thecatheter by sliding of the second tube attached to the catheter relativeto the first whilst keeping the catheter completely covered. Thus, whenin the advanced position, no portion of the catheter in contact withbody fluids can have been contaminated by physical contact with outsidecontaminants.

The multi-parameter catheter included in the apparatus has the variousfeatures and components described above. In particular, at least a partof the outer wail or sheath of the catheter is defined by a biphasicmembrane according to the invention, the space surrounding the sensorswithin the catheter is filled with a hydrophilic medium, and the cellsin the optical fiber sensors are filled with an indicator-containingmedium. Filling of the micropores of the biphasic membrane and the otherfilling operations described herein are achieved with the aid of avacuum rig apparatus as illustrated in FIG. 7 and 8 of the drawings.

The apparatus illustrated in FIG. 7 comprises a first vessel 80, whichin the preferred embodiment is a spherical bottle, made of glass ortransparent plastic, having an exit port 81 enabling it to be connectedto a second vessel 82. In the preferred embodiment the connectionbetween the first vessel and the second vessel is a tubular conduit 83having an arc-shaped profile and tapered ends 84, 85 which make afluid-tight connection with a female port 81 in the first vessel and afemale port 86 in the second vessel, respectively. The second vessel isa hollow tube having a proximal end terminating in the port 86 and adistal end 87 which is integral with a "U" shaped tube 88 having an opendistal end 89 which projects into a space defined by a third vessel 90.In the preferred embodiment the third vessel is substantially tubular inshape and the tube is perpendicular to the tubular second vessel. Thetubular third vessel is a reservoir for liquid and when the apparatus isused as described hereinafter liquid 91 is introduced into the reservoirup to a level just below the distal end 89 of the "U" tube. The distalend of the reservoir has a first port 92 which acts as a drain and issealed with a liquid-tight plug 93 when the apparatus is in use. Thereservoir also has a second port 94 through which it is connected to afourth vessel 95. The fourth vessel has a first port 96 which acts as anadditional drain and may be sealed with a plug 97; a second port 98through which liquid is introduced into the apparatus and which issealed with a plug 99; and a third port 100 which is adapted to beconnected to a vacuum line 101 through which a vacuum may be pulled onthe apparatus. A hook shaped trap 102 is located at the lower end of theentry port 98. This trap prevents liquid from being sucked back into thevacuum line when a vacuum is pulled. A tubular conduit 103 connects thesecond vessel to the fourth vessel and acts as a vent when a vacuum ispulled on the apparatus.

The vacuum rig apparatus is used for introducing a liquid into a spacedefined by a shaped article. Shaped articles of particular interestherein, all of which may be filled with the desired liquid medium by thevacuum rig apparatus of the invention, are the optical fiber pH and pCO₂sensors (where the liquid medium is a solution of gel and indicator),and the electrochemical pO₂ sensor (where the liquid medium is anelectrolyte solution), used in the multi-parameter catheter describedherein, the catheter itself and the biphasic membrane of the invention.For the purpose of illustration the operation of the vacuum rigapparatus will be described with reference to microporous hollow fibre(MPHF) used to form the biphasic membrane of the invention. A bundle ofMPHF, for example microporous polyethylene having a porosity of 40%, isplaced in the first vessel 80 of the apparatus in the upright positionas shown in FIG. 7 so that the distal end 2 containing the micropores tobe filled with liquid extend into and are suspended within the secondvessel 82, as shown in FIG. 8. The ports 92 and 96 are sealed with plugs93 and 97, respectively, and the reservoir 90 is filled, through port98, with the desired liquid 91, for example, a gelling solutioncontaining polyacrylamide, indicator and gelling agent, up to a leveljust below the distal end 89 of the "U" tube. The entry port 98 is thensealed with plug 99 and, with the apparatus still in the uprightposition, a vacuum is pulled on the apparatus through line 101 and port100. The vacuum is maintained until the liquid is fully degassed and themicropores in the MPHF are evacuated, usually about 15-20 minutes. Therig is then tilted to the position shown in FIG. 8 whereupon the liquid91 from the reservoir enters the distal end 89 of the "U" tube and runsdown the tube 88 and into the second vessel 82 where it surrounds thefibers and diffuses into the evacuated micropores, thus providing ahydrophilic infrastructure within a hydrophobic matrix.

The following working example illustrates in more detail the preparationof hydrophilic gel filled porous fibers according to the invention.

EXAMPLE

(A) Vacuum Filling Ethanol/Water

A 60/40 v/v solution of ethanol and ultra high purity (UHP) water wasprepared by mixing 60 ml. of ethanol and 40 ml. of water in a 100 ml.measuring cylinder. The solution was poured into the reservoir of avacuum rig as described herein. A bundle of sensors (about 50), boundwith polytetrafluoroethylene (PTFE) tape was loaded into the vacuum rigso that the distal ends of the sensors extended into the sensor-holdingvessel 82. The entry port of the vacuum rig was sealed and the vacuumline connected to the vacuum port. The vacuum line was opened, whileensuring that the needle valve inlet was closed, and a vacuum was pulleduntil a vacuum of 0-10 mbar was reached. The vacuum was held on thesolution until the liquid was fully degassed, about 15-20 minutes.

The vacuum rig was then tilted (FIG. 8) so that the solution poured intothe sensor-holding vessel and fully covered the complete length of theMPHF on all the sensors plus about 10-20 mm. above the butt-jointbetween the tubing 6 and the sheath 2 (FIG. 1). The rig was thenreturned to the upright position and the sensors immersed in ethanol fora further 5 minutes. The vacuum line was closed, the inlet valve fullyopened and the interior of the rig allowed to reach atmosphericpressure.

(B) Gelling Solution (Diffusion Fill)

Because of the hazardous nature of the solution used in this step thehandler should wear protective clothing, including gloves, goggles andface mask.

A 250 ml. flask is filled with a gelling solution comprising 15% w/wacrylamide monomer, 2.65% w/w methylene bisacrylamide cross-linkingagent, 7.65% w/w ammonium persulphate initiator, and 12% w/w indicator(for example, phenol red) in a phosphate buffered aqueous solutionadjusted to pH 3 with hydrochloric acid, and the solution was stirredwith an ultrasonic stirrer. The sensors, treated in step (A) above werenow transferred from the vacuum rig. Since the ethanol/water mixture isvolatile and the sensors can dry out very quickly, the sensors weretransferred to a vessel containing UHP water. The sensors were immersedin the gelling solution such that the full length of the MPHF wassubmerged, and the sensors were held in the gelling solution for twohours.

(C) Set Gel

Again protective clothing should be worn by the handler.

A heated water bath was switched on until the temperature reached 40°±1°C., the temperature being checked with a thermometer. A number of testtubes were filled with a solution of TMED (N,N,N',N'-tetramethylethylenediamine), and placed in holders in the water bath.

The sensors were removed individually from the gelling solution and eachsensor was dipped into an individual test tube containing TMED solutionfor four minutes, ensuring that the MPHF portion of the sensor was fullyimmersed in the TMED solution. Each of the sensors was then removed fromthe TMED solution and transferred directly into an acid conditioningsolution of about 17% w/v sodium dihydrogen orthophosphate at a pH of4.5 and held in the solution for about 30 minutes. When all of thegelled portions of the sensors were a solid yellow color they were readyfor transfer to the cure bath.

(D) Curing

The sensors were removed individually from the acid conditioningsolution. A hanger was attached to the tip of each sensor and thesensors were racked with the MPHF portion fully submerged in thetonometer solution, i.e. a 12 m/M molar solution of sodium carbonate andsodium sulphate. During this operation the circulation system is runconstantly to ensure that there was no microbiological contamination ofthe cure bath.

The temperature of the cure bath was set to 50°-55° C. and maintained atthis temperature for not less than 2 hours.

The cured sensor was mounted in a tonometer which was then sealed in apackage where it was sterilized and stored until required for use.

We claim:
 1. A multi-parameter catheter for the in vivo determination of multiple parameters in a patient's blood comprising an elongated tube with a distal hollow chamber having a wall terminating in a distal end, the wall of said chamber being defined at least in part by a biphasic membrane which is a microporous polyethylene tube having micropores which are filled with a polyacrylamide hydrogel which allows the passage of water-bound ions, said chamber containing a plurality of sensors mounted sequentially from said distal end within a polyacrylamide hydrogel, the sequentially mounted sensors comprising, in sequence from the distal end of the chamber, an optical fiber pH sensor, an optical fiber pCO₂ sensor, a thermocouple temperature sensor and a pO₂ sensor, and the distal end of the chamber being sealed by a solid plug made from a thermoplastic polymer.
 2. A catheter according to claim 1, in which the biphasic membrane has a proximal end which forms a butt-joint with a sheath of non-porous polymeric tubing which covers a proximal portion of the catheter.
 3. A catheter according to claim 2, in which a proximal portion of the catheter is back-filled with a radiation-opaque coating over the non-porous polymeric tubing.
 4. An apparatus for the in vivo determination of multiple parameters in a patient's blood comprising, in combination, a catheter according to claim 5 and a device for introducing said catheter into a patient's blood vessel, said device comprising a first elongated flexible hollow tube having a distal end, a proximal end and a distal portion terminating in said distal end, a second elongated extension tube having a distal end and a proximal end concentrically mounted within the distal portion of said first tube for telescopic extension beyond the distal end of said first tube and retraction within said first tube, so that when the second tube is fully extended it completely envelopes the catheter and when it is retracted the catheter is exposed, the device also including locking means for locking the second tube in the extended or retracted position as desired and means for introducing a sterile liquid within said second tube to surround the catheter when it is within the tube.
 5. An apparatus according to claim 4, in which the introducer device has a connector at the proximal end thereof, which connector is attached to leads from each sensor of the catheter.
 6. An apparatus according to claim 4, which includes a tonometer for storing and calibrating the sensor-containing catheter prior to use, which tonometer is attached to the distal end of the introducer device through a male luer lock with a rotatable collar, the said catheter being in the extended position beyond the distal end of the second tube of the introducer device for accommodation within the tonometer.
 7. An apparatus according to claim 4, in which the means for introducing a sterile liquid within the second tube is a Y-junction mounted on the second tube at a position adjacent a proximal end of the catheter when the catheter is fully retracted, one arm of the Y extending outwardly from the second tube and terminating in a male luer lock obturator capable of being attached to a source of sterile liquid for introduction into the second tube and the other arm of the Y lying coaxially along the second tube and terminating proximally in a rotatable clamp nut which provides the locking means for locking the second tube in a desired position relative to the first tube and sealing the second tube around the catheter.
 8. An apparatus according to claim 4 which includes means for securing the catheter against the body of the patient. 